Antibody-mediated antigen tethering as a regulator of germinal-center B cell affinity and diversity

To optimally protect a host, the adaptive immune system must generate antibodies (Abs) that bind the pathogen with high affinity, yet are diverse enough to protect against potential escape mutations. How the immune system can steer between affinity and diversity remains an open question. During the immune response, B cells inside germinal centers (GCs) compete for survival based on their ability to extract antigen from the surface of specialized presenting cells called follicular dendritic cells (FDCs). Curiously, FDCs tether antigen via not one, but two qualitatively distinct routes: direct tethering, in which the linking protein is covalently bound to the Ag, and indirect, Ab-mediated tethering, in which the linking protein is an Ab itself. Using agent-based simulations motivated by the biophysics of Ag extraction, we suggest that the dual-tethering system can improve the robustness of affinity maturation, and may provide a mechanism to steer the balance between affinity and diversity of the GC B cell population. Our model is consistent with experimental observations reporting low-affinity but high-diversity GCs in the absence of Fc γ R, a key Ab-tethering receptor on FDCs.